A PASSIVE TRANSFER MODEL OF THE ORGAN-SPECIFIC AUTOIMMUNE-DISEASE, BULLOUS PEMPHIGOID, USING ANTIBODIES GENERATED AGAINST THE HEMIDESMOSOMAL ANTIGEN, BP180
A PASSIVE TRANSFER MODEL OF THE ORGAN-SPECIFIC AUTOIMMUNE-DISEASE, BULLOUS PEMPHIGOID, USING ANTIBODIES GENERATED AGAINST THE HEMIDESMOSOMAL ANTIGEN, BP180
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DOI：
10.1172/jci116856
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发表时间：
1993-11-01
影响因子：
15.9
通讯作者：
GIUDICE, GJ
中科院分区：
文献类型：
--
作者：
LIU, Z;DIAZ, LA;GIUDICE, GJ
与人类皮肤病大疱性类天疱疮和妊娠疱疹相关的表皮下水疱被认为是IgG自身抗体介导的过程;然而，先前试图证明患者自身抗体的致病性的尝试一直不成功。与这些起泡性疾病相关的免疫显性和潜在致病性表位最近被定位到人表皮抗原BP 180的细胞外结构域。与该明确定义的抗原位点反应的患者自身抗体未能与该自身抗原的鼠形式交叉反应，因此无法在常规被动转移小鼠模型中测定致病性。作为替代方案，针对与人BP 180自身抗体反应性位点同源的鼠BP 180蛋白的片段产生兔多克隆抗体，并将其被动转移到新生BALB / c小鼠中。注射的动物发生了表皮下起泡疾病，在临床、组织学和免疫学水平上与大疱性类天疱疮和妊娠疱疹非常相似。因此，识别人BP 180胞外域的自身抗体可能在大疱性类天疱疮和妊娠疱疹的发病机制中起起始作用。
Subepidermal blistering associated with the human skin diseases bullous pemphigoid and herpes gestationis has been thought to be an IgG autoantibody-mediated process; however, previous attempts to demonstrate the pathogenicity of patient autoantibodies have been unsuccessful. An immunodominant and potentially pathogenic epitope associated with these blistering diseases has recently been mapped to the extracellular domain of a human epidermal antigen, BP180. Patient autoantibodies that react with this well-defined antigenic site failed to crossreact with the murine form of this autoantigen and thus could not be assayed for pathogenicity in a conventional passive transfer mouse model. As an alternative, rabbit polyclonal antibodies were generated against a segment of the murine BP180 protein homologous with the human BP180 autoantibody-reactive site and were passively transferred into neonatal BALB / c mice. The injected animals developed a subepidermal blistering disease that closely mimicked bullous pemphigoid and herpes gestationis at the clinical, histological, and immunological levels. Autoantibodies that recognize the human BP180 ectodomain are therefore likely to play an initiatory role in the pathogenesis of bullous pemphigoid and herpes gestationis.